Activatable CRISPR Transcriptional Circuits Generate Functional RNA for mRNA Sensing and Silencing
CRISPR‐dCas9 systems that are precisely activated by cell‐specific information facilitate the development of smart sensors or therapeutic strategies. We report the development of an activatable dCas9 transcriptional circuit that enables sensing and silencing of mRNA in living cells using hybridizati...
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| Veröffentlicht in: | Angewandte Chemie International Edition 2020-10, Vol.59 (42), p.18599-18604 |
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| creator | Ying, Zhan‐Ming Wang, Fenglin Chu, Xia Yu, Ru‐Qin Jiang, Jian‐Hui |
| description | CRISPR‐dCas9 systems that are precisely activated by cell‐specific information facilitate the development of smart sensors or therapeutic strategies. We report the development of an activatable dCas9 transcriptional circuit that enables sensing and silencing of mRNA in living cells using hybridization‐mediated structure switching for gRNA activation. The gRNA is designed with the spacer sequence blocked by a hairpin structure, and mRNA hybridization induces gRNA structure switching and activates the transcription of reporter RNA. An mRNA sensor developed using a light‐up RNA reporter shows high sensitivity and fast‐response imaging of survivin mRNA in cells under drug treatments and different cell lines. Furthermore, a feedback circuit is engineered by incorporating a small hairpin RNA in the reporter RNA, demonstrating a smart strategy for dynamic sensing and silencing of survivin with induced tumor cell apoptosis. This circuit illustrates a broadly applicable platform for the development of cell‐specific sensing and therapeutic strategies.
An activatable dCas9 transcriptional circuit is designed utilizing the strategy of hybridization‐mediated structure switching for gRNA activation. The designed circuit enables sensing and silencing of mRNA in living cells. |
| doi_str_mv | 10.1002/anie.202004751 |
| format | Article |
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An activatable dCas9 transcriptional circuit is designed utilizing the strategy of hybridization‐mediated structure switching for gRNA activation. The designed circuit enables sensing and silencing of mRNA in living cells.</description><edition>International ed. in English</edition><identifier>ISSN: 1433-7851</identifier><identifier>EISSN: 1521-3773</identifier><identifier>DOI: 10.1002/anie.202004751</identifier><identifier>PMID: 32633466</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Apoptosis ; Biosensing Techniques ; biosensors ; CRISPR ; CRISPR-Cas Systems - genetics ; CRISPR-dCas9 ; Feedback circuits ; Functional morphology ; Gene Silencing ; gRNA ; HeLa Cells ; Humans ; Hybridization ; light-up RNA ; Microscopy, Confocal ; mRNA ; Nucleic Acid Hybridization ; Plasmids - genetics ; Plasmids - metabolism ; RNA, Guide, CRISPR-Cas Systems - metabolism ; RNA, Messenger - analysis ; RNA, Messenger - metabolism ; RNA, Small Interfering - metabolism ; Smart sensors ; Survivin ; Survivin - genetics ; Switching ; theranostics ; Transcription ; Transcriptional Activation</subject><ispartof>Angewandte Chemie International Edition, 2020-10, Vol.59 (42), p.18599-18604</ispartof><rights>2020 Wiley‐VCH GmbH</rights><rights>2020 Wiley-VCH GmbH.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4101-c77336311380e2f5d51eeda59282d48a80fa3e1bdc75d67a0df11f4ded3a7123</citedby><cites>FETCH-LOGICAL-c4101-c77336311380e2f5d51eeda59282d48a80fa3e1bdc75d67a0df11f4ded3a7123</cites><orcidid>0000-0003-1594-4023</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fanie.202004751$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fanie.202004751$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32633466$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ying, Zhan‐Ming</creatorcontrib><creatorcontrib>Wang, Fenglin</creatorcontrib><creatorcontrib>Chu, Xia</creatorcontrib><creatorcontrib>Yu, Ru‐Qin</creatorcontrib><creatorcontrib>Jiang, Jian‐Hui</creatorcontrib><title>Activatable CRISPR Transcriptional Circuits Generate Functional RNA for mRNA Sensing and Silencing</title><title>Angewandte Chemie International Edition</title><addtitle>Angew Chem Int Ed Engl</addtitle><description>CRISPR‐dCas9 systems that are precisely activated by cell‐specific information facilitate the development of smart sensors or therapeutic strategies. We report the development of an activatable dCas9 transcriptional circuit that enables sensing and silencing of mRNA in living cells using hybridization‐mediated structure switching for gRNA activation. The gRNA is designed with the spacer sequence blocked by a hairpin structure, and mRNA hybridization induces gRNA structure switching and activates the transcription of reporter RNA. An mRNA sensor developed using a light‐up RNA reporter shows high sensitivity and fast‐response imaging of survivin mRNA in cells under drug treatments and different cell lines. Furthermore, a feedback circuit is engineered by incorporating a small hairpin RNA in the reporter RNA, demonstrating a smart strategy for dynamic sensing and silencing of survivin with induced tumor cell apoptosis. This circuit illustrates a broadly applicable platform for the development of cell‐specific sensing and therapeutic strategies.
An activatable dCas9 transcriptional circuit is designed utilizing the strategy of hybridization‐mediated structure switching for gRNA activation. The designed circuit enables sensing and silencing of mRNA in living cells.</description><subject>Apoptosis</subject><subject>Biosensing Techniques</subject><subject>biosensors</subject><subject>CRISPR</subject><subject>CRISPR-Cas Systems - genetics</subject><subject>CRISPR-dCas9</subject><subject>Feedback circuits</subject><subject>Functional morphology</subject><subject>Gene Silencing</subject><subject>gRNA</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Hybridization</subject><subject>light-up RNA</subject><subject>Microscopy, Confocal</subject><subject>mRNA</subject><subject>Nucleic Acid Hybridization</subject><subject>Plasmids - genetics</subject><subject>Plasmids - metabolism</subject><subject>RNA, Guide, CRISPR-Cas Systems - metabolism</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Smart sensors</subject><subject>Survivin</subject><subject>Survivin - genetics</subject><subject>Switching</subject><subject>theranostics</subject><subject>Transcription</subject><subject>Transcriptional Activation</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM9LwzAYhoMoOn9cPUrAi5fOfEnTdscxNh3IlG33kiVfJdKlM2mV_fdmbCp48fS9H3nykjyEXAPrA2P8XjmLfc44Y2ku4Yj0QHJIRJ6L45hTIZK8kHBGzkN4i3xRsOyUnAmeCZFmWY-shrq1H6pVqxrpaD5dvMzp0isXtLeb1jZO1XRkve5sG-gDOvSqRTrpnD4czmdDWjWerndhgS5Y90qVM3Rha3Q6bpfkpFJ1wKvDvCDLyXg5ekyenh-mo-FTolNgkOj4ZpEJAFEw5JU0EhCNkgNecJMWqmCVEggro3NpslwxUwFUqUEjVA5cXJC7fe3GN-8dhrZc26CxrpXDpgslTzkAMClkRG__oG9N5-NvdlRa8CwfCIhUf09p34TgsSo33q6V35bAyp38cie__JEfL9wcarvVGs0P_m07AoM98BndbP-pK4ez6fi3_AswVI9e</recordid><startdate>20201012</startdate><enddate>20201012</enddate><creator>Ying, Zhan‐Ming</creator><creator>Wang, Fenglin</creator><creator>Chu, Xia</creator><creator>Yu, Ru‐Qin</creator><creator>Jiang, Jian‐Hui</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1594-4023</orcidid></search><sort><creationdate>20201012</creationdate><title>Activatable CRISPR Transcriptional Circuits Generate Functional RNA for mRNA Sensing and Silencing</title><author>Ying, Zhan‐Ming ; Wang, Fenglin ; Chu, Xia ; Yu, Ru‐Qin ; Jiang, Jian‐Hui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4101-c77336311380e2f5d51eeda59282d48a80fa3e1bdc75d67a0df11f4ded3a7123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Apoptosis</topic><topic>Biosensing Techniques</topic><topic>biosensors</topic><topic>CRISPR</topic><topic>CRISPR-Cas Systems - genetics</topic><topic>CRISPR-dCas9</topic><topic>Feedback circuits</topic><topic>Functional morphology</topic><topic>Gene Silencing</topic><topic>gRNA</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Hybridization</topic><topic>light-up RNA</topic><topic>Microscopy, Confocal</topic><topic>mRNA</topic><topic>Nucleic Acid Hybridization</topic><topic>Plasmids - genetics</topic><topic>Plasmids - metabolism</topic><topic>RNA, Guide, CRISPR-Cas Systems - metabolism</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Smart sensors</topic><topic>Survivin</topic><topic>Survivin - genetics</topic><topic>Switching</topic><topic>theranostics</topic><topic>Transcription</topic><topic>Transcriptional Activation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ying, Zhan‐Ming</creatorcontrib><creatorcontrib>Wang, Fenglin</creatorcontrib><creatorcontrib>Chu, Xia</creatorcontrib><creatorcontrib>Yu, Ru‐Qin</creatorcontrib><creatorcontrib>Jiang, Jian‐Hui</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Angewandte Chemie International Edition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ying, Zhan‐Ming</au><au>Wang, Fenglin</au><au>Chu, Xia</au><au>Yu, Ru‐Qin</au><au>Jiang, Jian‐Hui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activatable CRISPR Transcriptional Circuits Generate Functional RNA for mRNA Sensing and Silencing</atitle><jtitle>Angewandte Chemie International Edition</jtitle><addtitle>Angew Chem Int Ed Engl</addtitle><date>2020-10-12</date><risdate>2020</risdate><volume>59</volume><issue>42</issue><spage>18599</spage><epage>18604</epage><pages>18599-18604</pages><issn>1433-7851</issn><eissn>1521-3773</eissn><abstract>CRISPR‐dCas9 systems that are precisely activated by cell‐specific information facilitate the development of smart sensors or therapeutic strategies. We report the development of an activatable dCas9 transcriptional circuit that enables sensing and silencing of mRNA in living cells using hybridization‐mediated structure switching for gRNA activation. The gRNA is designed with the spacer sequence blocked by a hairpin structure, and mRNA hybridization induces gRNA structure switching and activates the transcription of reporter RNA. An mRNA sensor developed using a light‐up RNA reporter shows high sensitivity and fast‐response imaging of survivin mRNA in cells under drug treatments and different cell lines. Furthermore, a feedback circuit is engineered by incorporating a small hairpin RNA in the reporter RNA, demonstrating a smart strategy for dynamic sensing and silencing of survivin with induced tumor cell apoptosis. This circuit illustrates a broadly applicable platform for the development of cell‐specific sensing and therapeutic strategies.
An activatable dCas9 transcriptional circuit is designed utilizing the strategy of hybridization‐mediated structure switching for gRNA activation. The designed circuit enables sensing and silencing of mRNA in living cells.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32633466</pmid><doi>10.1002/anie.202004751</doi><tpages>6</tpages><edition>International ed. in English</edition><orcidid>https://orcid.org/0000-0003-1594-4023</orcidid></addata></record> |
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| subjects | Apoptosis Biosensing Techniques biosensors CRISPR CRISPR-Cas Systems - genetics CRISPR-dCas9 Feedback circuits Functional morphology Gene Silencing gRNA HeLa Cells Humans Hybridization light-up RNA Microscopy, Confocal mRNA Nucleic Acid Hybridization Plasmids - genetics Plasmids - metabolism RNA, Guide, CRISPR-Cas Systems - metabolism RNA, Messenger - analysis RNA, Messenger - metabolism RNA, Small Interfering - metabolism Smart sensors Survivin Survivin - genetics Switching theranostics Transcription Transcriptional Activation |
| title | Activatable CRISPR Transcriptional Circuits Generate Functional RNA for mRNA Sensing and Silencing |
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